NCT07410494

Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors

A Phase 1/2, Open-Label, Biomarker-Driven Study of Allogeneic Donor-Derived CAR-NK Cells With Antigen Selection by Tissue Biopsy and/or Liquid Biopsy Profiling in Participants With Relapsed/Refractory Advanced Solid Tumors (Single-Target vs Dual-Target Strategy)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 85 (estimated)
• Sponsor: Essen Biotech · Academic / Other
• Sex: All
• Age: 8 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This Phase 1/2 study evaluates the safety, feasibility, and preliminary anti-tumor activity of allogeneic donor-derived CAR-NK cells in participants with advanced solid tumors. The CAR target antigen is selected for each participant after tumor profiling using a tissue biopsy and/or liquid biopsy. Participants will receive either a single-target or dual-target CAR-NK product based on the antigen profile.

Detailed description

This is an open-label, biomarker-driven adoptive cell therapy study. Screening / Target Selection (Precision Step): Participants undergo tumor antigen profiling using: Tissue biopsy (preferred when safely feasible), and/or Liquid biopsy (e.g., circulating tumor DNA plus circulating tumor cells/exosome protein assay, as available in the platform). Antigen profiling determines eligibility and assigns participants to: Single-target CAR-NK if one antigen meets positivity thresholds, or Dual-target CAR-NK if two antigens meet thresholds or if heterogeneity is suspected. Pre-specified target menu : TROP2, Mesothelin (MSLN), B7-H3 (CD276), HER2, EGFR, GD2, Claudin18.2, GPC3, PSMA ("Target menu" can be expanded in amendments.) Cell Source / Manufacturing Concept: NK cells are obtained from a healthy allogeneic donor (unrelated or partially matched per site policy). Donor NK cells are collected by leukapheresis, activated/expanded, and genetically modified to express: a single CAR (Arm A) or a dual CAR / dual-target construct (Arm B). Final product is cryopreserved and released after sterility/identity/potency testing. Conditioning \& Treatment: Participants receive lymphodepleting chemotherapy followed by CAR-NK infusion(s). Many CAR-NK solid-tumor trials use conditioning regimens such as fludarabine and cyclophosphamide before infusion. Optional cytokine support (e.g., low-dose IL-2) may be used per protocol to support NK persistence, consistent with approaches used in some CAR-NK studies. Follow-up: Intensive safety monitoring during the first 28 days. Tumor imaging at protocol-defined intervals. Correlative studies including CAR-NK persistence and ctDNA dynamics.

Conditions

• Cancer
• Breast Cancer
• Non-Small Cell Lung Cancer (NSCLC)
• Colorectal Cancer (Locally Advanced or Metastatic)
• Prostate Cancer - Recurrent
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Ovarian Cancer
• Glioblastoma
• Melanoma (Skin Cancer)
• Acute Myeloid Leukemia (AML)
• Non Hodgkin Lymphoma
• Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma
• Liver Cancer

Interventions

Type	Name	Description
BIOLOGICAL	EB-SELECT Single-Target CAR-NK Cells	Donor-derived CAR-NK cells expressing a single CAR selected from the target menu. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion. Similar conditioning drugs are used in CAR-NK solid tumor trials.
BIOLOGICAL	Dual-Target Antigen-Selected CAR-NK	Participants whose profiling identifies two actionable antigens, or strong evidence of antigen heterogeneity. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion . Similar conditioning drugs are used in CAR-NK solid tumor trials.

Timeline

• Start date: 2026-02-01
• Primary completion: 2027-12-28
• Completion: 2028-12-28
• First posted: 2026-02-13
• Last updated: 2026-02-18

Locations

1 site across 1 country: China